Lower eyelid retraction: a minimal incision surgical approach to retractor lysis

Lower eyelid retraction associated with prior blepharoplasty, trauma, or other conditions is a challenging problem for the ophthalmic surgeon. We describe a procedure involving tightening the lower eyelid and supraplacing the lateral canthus in combination with in-glove lysis of the lower eyelid retractors and scar tissue. This is accomplished through a small lateral incision. To date, we have treated over 200 eyelids using this technique with excellent results. We recommend this technique for the treatment of mild to moderate degrees of lower eyelid retraction.     

Pulsed CO2 laser tissue ablation: effect of tissue type and pulse duration on thermal damage

Tissue removal by infrared lasers is accompanied by thermal damage to nonablated tissue. The extent of thermal damage can be controlled by a choice of laser wavelength, irradiance, and exposure duration. The effect of exposure duration has been studied in vivo by using CO2 lasers with pulse widths that vary from 2 microseconds to 50 msec. Pulse widths of 50 msec, typical of a shuttered, continuous-wave CO2 laser, produce damage regions 750 micron wide in normal guinea pig skin; the use of a 2-microseconds-long pulse reduced this damage zone to as little as 50 micron. Using 2-microseconds-long pulses, in vitro studies showed that the minimum zone of thermal damage varied significantly with tissue type. The thermal denaturation of these tissues has been studied and correlated with damage. The effect of denaturation temperature and pulse duration on the width of the damage zone is explained by a simple model.     

Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human saphenous vein.

1. Angiotensin II (AII) causes contraction of isolated rings of human saphenous vein, responses that are attenuated by the presence of functional endothelium. In this study, we have investigated the mechanisms controlling the release by AII of two endothelial-derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO). 2. Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6-oxo-PGF1 alpha) and of NO (as cyclic GMP). Inhibitors of cyclo-oxygenase (COX; piroxicam) or NO synthase (NOS; L-NAME), were added to the system to determine the influence of endogenous prostaglandins and NO on both myotropic and biochemical responses. Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of these relaxants were added, during inhibition of their endogenous release. 3. Contractions of the rings of saphenous vein in response to AII (1-100 nM) were unaffected by treatment with either piroxicam (5 microM) or L-NAME (200 microM) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII. 4. Biochemical analyses revealed that during stimulation by AII, levels of PGI2 and NO were enhanced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can inhibit NO synthesis. 5. Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively. 6. These results demonstrate the presence, in human saphenous vein, of a mechanism which ensures that levels of vasodilatation are maintained through a compensatory increase in one relaxant agonist when output of the other is decreased. If present in vivo such a mechanism would be important in maintaining saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in degeneration of graft function.     

De-regulation of endogenous retrotransposons in mouse mammary carcinomas of diverse etiologies

Of the several families of endogenous retrovirus-like elements present in the mouse genome, only mouse mammary tumor virus has been analyzed for its role in mammary carcino-genesis. Very little is known about the expression and activities of other retro-elements in normal and malignant mammary epithelium. We have begun investigating the possible involvement of the 3 retrotransposons, intracisternal A particles (IAPs), murine-leukemia-virus-related (MuLVr) elements, and VL30 sequences, in neoplastic progression of the mammary gland in BALB/c mice. The purpose of the present study was to determine which of these elements was active in primary mammary carcinomas induced by chemical, hormonal and viral agents. Each of these cancers had aberrant expression of at least one of the latter retrovirus-like components. IAP and/or MuLVr sequences were over-expressed 3 to 100-fold in most of the tumors as compared with normal mammary tissue, whereas VL30 expression was markedly decreased by 5- to 35-fold in almost all of the neoplasms. Our results thus demonstrate that substantial changes in the expression of one or more of these 3 families of endogenous retrotransposons are triggered during mouse mammary tumorigenesis, regardless of etiology. Direct involvement of lAPs and MuLVr elements in neoplastic progression by transposition and insertional mutagenesis in the genome of several hematopoietic cell types has already been demonstrated. Their elevated expression in many mammary carcinomas suggests that these retrotransposons may also be potential participants in some pathways of mouse mammary carcinogenesis.     

Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae

The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Quality of Life in Progressive Ovarian Cancer

When ovarian cancer progresses, goals change from cure to prolongation of life with the best possible quality for the patient. Criteria for futility must be established to guide the transition from active to palliative management. Pain control can be achieved by following established WHO guidelines. Continued education of the medical community, legislators, and the public is needed to assure pain control for the cancer patient. Limited surgery or radiation can be used to control symptoms from locally progressive disease. Other symptoms to be actively controlled include nausea and vomiting, nutrition, hydration, and fatigue. Support services, including home services, psychological counseling, and nutritional support need funding for both home and hospital settings. Quality of life assessment must be as specific as possible and address the patient's concerns by self-assessment techniques. Funding must be provided to develop specific quality of life tools and to then apply them clinically, both as part of research protocols and to assess success of palliative care.